SIRT1, the”Longevity gene” cures Alzheimer’s in mice

Scientists from MIT have discovered a method to dramatically reduce the loss of memory and learning ability in mice with a version of Alzheimer’s disease, potentially offering a new approach for tackling the illness in humans.

A group of biologists at MIT say they have obtained evidence from an animal study that the SIRT1 pathway can be used to successfully treat Alzheimer’s. The researchers achieved the result by working with a gene, SIRT1, in the mouse brain. The gene regulates the production of a class of proteins known as sirtuin one.

In a study of mice modeled to suffer from Alzheimer’s while producing higher levels of sirtuin one, the scientists found that the rodents retained both memory and learning abilities, warding off the disease.

Sometimes described as the “longevity gene,” SIRT1 has become the focus of intense research in recent years. Studies have shown that a highly calorie-restricted diet can turn on the gene and thereby increase longevity in everything from yeast to mice.

Similarly, a compound called resveratrol, found in red wine, also might switch on the gene, and tap the brakes on aging, at least in animals. Drug companies, including Cambridge-based Sirtris Pharmaceuticals Inc., a subsidiary of GlaxoSmithKline PLC, have been developing medications for diabetes and metabolic disorders based on this idea.

SIRT1 is also involved in learning and memory, according to two other recent papers. One was published in Nature earlier this month, led by MIT neuroscientist Li-Huei Tsai, and the other in the current issue of the Journal of Neuroscience, led by University of Southern California biochemist Valter D. Longo.

“This is the first demonstration that the SIRT1 pathway can mitigate Alzheimer’s,” Leonard Guarente, a biologist at MIT, tells the Wall Street Journal. And mice engineered without SIRT1 quickly succumbed to the disease. When a certain protein is broken into fragments, it creates amyloid plaques that are a biomarker of Alzheimer’s. But it’s believed that sirtuin one can break the fragments into harmless particles, helping to avert the disease, which strikes one in three people who reach the age of 80.

It will be a long road from the new SIRT1 findings to any medications for people with Alzheimer’s, said Dr. Howard Fillit, executive director of the Alzheimer’s Drug Discovery Foundation, a charity devoted to accelerating drug development.

“These are very interesting science findings in mice,’’ Fillit said in an e-mail. “But scientists have been able to cure genetically modified mice with features related to Alzheimer’s disease 150 to 200 times, “and we still don’t have a drug for human beings to take.’’